Thread by @gerdosi

1/ I have a thread about natural immunity to SARS-CoV-2, but I was asked to do a comparison with vaccine induced immunization. Interestingly, deep analysis of the two is largely missing. A recent study will do the job,
science.sciencemag.org/content/early/…

https://twitter.com/gerdosi/status/1343565534512742402?s=20

2/ but we need to focus on results, not conclusions, because even though the study was designed to compare the two types of immunization, plus added the effect of a booster jab on top of infection, the interpretation is a bit twisted to mostly compare the 2 jab scenarios.

3/ Quote:
"Three individuals who previously showed a response, despite lack of laboratory evidence for infection (therefore presumably a cross-reactive response to an endemic human coronavirus) showed an unchanged or decreased [T cell] response to spike after vaccination."

4/ Apparently, in some cases, vaccination can decrease T cell response to real antigen exposure, which is needless to say, not good. A preprint described the phenomenon earlier, although only following the second, so-called booster, jab:

https://twitter.com/gerdosi/status/1377020037043658752?s=20

5/ Next quote:
"Twenty of 22 vaccinated naïve individuals had detectable S1 specific ASC comprising 0.02% to 1.54% of the memory B cell (MBC) pool. By comparison, all vaccinated post infection individuals had detectable S1 specific ASCs (1.90–50% of MBC pool)."

6/ This boost seems totally unnecessary in the vast majority of people, perhaps with the exception of the lowest end of the spectrum (non-responders). Potential harms of 50 % !!! of all ASCs dedicated to a single subunit of a single virus? Certainly not normal.

7/ On to the next part in the paper: "Vaccinated naïve individuals made a lower nAb response to WT virus than seen following natural infection at 16–18 weeks" Finally, a concrete comparison. It shows that natural infection induced immunity is at least as good as vaccination.

8/ Next quote: "there was a significantly enhanced nAb response in vaccinated post infection individuals compared with the vaccinated naïve group (Fig. 1G), the mean value being 25,273 compared to 420, that is, a 60-fold increase."
Is it a useful bump? Is the higher the better?

9/ Move on to "The data in Fig. 1 indicate that there is a strong prime-boosting effect of prior infection on single dose vaccination. Augmentation is seen more strongly in MBC frequency, anti-RBD, and nAb responses than for T cell response frequency.

10/ …Furthermore, there was no correlation between S1 ASC frequency and T cell response frequency (Fig. 1H). There is, however, a correlation between S1 ASC and RBD antibody titers"

11/ This finding suggests that the body reacts to vaccination after infection as if there was an acute reinfection.
It is not universal "boosting of immunity", just triggering Ab secretion from existing (and memory) cells.

12/ Seems counterproductive, except for Pfizer shareholders and executives?

Next quote: "The majority of SARS-CoV-2 immune naïve individuals made no nAb response to the B.1.1.7 (18/20) and B.1.351 (17/20) variants after single dose vaccination.

13/ …In contrast, almost all vaccinated post infection individuals made a strong nAb response to the B.1.1.7 (24/24) and B.1.351 (23/24) variants after a single dose vaccination with a 46-fold (B.1.1.7) and 63-fold (B.1.351) increase in mean nAb IC50"

14/ I'm confident that this is what happens upon reexposure to the virus, e.g. a variant. too. So what is the point of the booster again? Confirm the effect with virus and forget the excess jab.

15/ I am ready to volunteer, but you'll need an uncommon strain, because most likely I have already been exposed to the B117.

"Worryingly, after single dose vaccination, 90% (18/20) of vaccinated naïve individuals showed no detectable nAbs (IC50 < 50) against B.1.1.7"

16/ Defending the vaccine here, but it's not necessarily worrying. There is clearly no 90 % breakthrough rate of B117 in 3w+ primer vaccinated people. This is the striking problem of the unjustified strong focus on systemic antibodies in a fundamentally respiratory infection.

17/ Let's jump to the part "We initially looked at T cell responses following natural infection and found that at 16–18 weeks post infection, the N501Y mutation appeared to have no substantial differential impact on the T cell response (Fig. 2F), unlike nAb recognition."

18/ The authors also get it. That's why we have T cells, these can help refine Ab responses upon "variant" exposure. Miraculously, it already works in vaccinated people, despite the much narrower antigen range used.

19/ Apparently, the full spike is a long enough polypeptide sequence to provide many antigens for T cell receptors.

Next one, please.

20/ "vaccinated naïve individuals made an anti S1 RBD Ab response with a mean titer of about 100 U/ml at d22 (±2d) after vaccination, roughly equivalent to the mean peak Ab response after natural infection.

21/ …However, the spike T cell response after one dose was lower than after natural infection, and for 30% of vaccinees no response could be measured."
One jab is clearly inferior to natural infection. No response in 30 % sounds too high a proportion?

22/ A long quote is imminent, beware and pay attention please. "It is striking that the high IC50 titers in those vaccinated after infection provide such a large protective margin that responses to authentic B.1.1.7 and B.1.351variants are also high.

23/ …In contrast, nAb responses in individuals several months on from mild infection show much lower IC50s against B.1.1.7 and B.1.351, often <100. Similarly, the majority of responses in naïve individuals after one dose show weak recognition of B.1.1.7 and B.1.351.

24/ This finding indicates potentially poor protection against B.1.1.7 and B.1.351 in individuals who have experienced natural infection or who have only had one vaccine dose."

Firstly, it is not striking, rather expected.

25/ As suggested above, this is likely a normal response to reinfection. At least the body percieves the reappearance of antigens as re-exposure. Secondly, this finding still does not indicate poor protection against the mentioned variants.

26/ Perhaps it takes a day or two more and mild instead of no symptoms, but it's highly unlikely that the vast majority of people would experience variant infection the same way as an immune naïve individual.

27/ Last quote: "second dose vaccination in one dose vaccinated post infection individuals offers no additional enhancement."
A second "booster" for a previously infected person was even shown to suppress cellular immunity, which sounds straight harmful. See quote tweet in 4/.

28/ TL;DR
Natural infection induced immunity is typically at least as robust as the one elicited by double vaccination, but the former protects more effectively against emerging variants. Moreover, level of systemic Ab is not necessarily the best benchmark to use.
/End

Extending evidence base with this preprint. On a side note, time since immunization, whether via infection or vaccine, is an important factor that has to be taken into consideration when comparisons are made.

https://twitter.com/andrewbostom/status/1392450677591445507

Adding these intriguing findings.

https://twitter.com/gerdosi/status/1394985781106724871

Lifelong protection by bone marrow plasma cells after mild course of COVID-19.

https://twitter.com/gerdosi/status/1397132832770768905?s=20

This study surely belongs here.

https://twitter.com/gerdosi/status/1400459537149153289